Dynamic modulation of theta-gamma coupling during rapid eye movement sleep

Theta phase modulates gamma amplitude in hippocampal networks during spatial navigation and rapid eye movement (REM) sleep. This cross-frequency coupling has been linked to working memory and spatial memory consolidation; however, its spatial and temporal dynamics remains unclear. Here, we first investigate the dynamics of theta-gamma interactions using multiple frequency and temporal scales in simultaneous recordings from hippocampal CA3, CA1, subiculum, and parietal cortex in freely moving mice. We found that theta phase dynamically modulates distinct gamma bands during REM sleep. Interestingly, we further show that theta-gamma coupling switches between recorded brain structures during REM sleep and progressively increases over a single REM sleep episode. Finally, we show that optogenetic silencing of septohippocampal GABAergic projections significantly impedes both theta-gamma coupling and theta phase coherence. Collectively, our study shows that phase-space (i.e. cross-frequency coupling) coding of information during REM sleep is orchestrated across time and space consistent with region-specific processing of information during REM sleep including learning and memory. Significance Classical descriptions of sleep-related brain activity using low spatial resolution electroencephalography led to the distinction between non-rapid eye movement (NREM) and REM (or paradoxical) sleep. Yet, local brain activity during each of these states is characterized by circuit-specific oscillations (slow waves, spindles, and theta). In this study, we show that theta-gamma cross-frequency coupling (CFC) in the hippocampus is dynamically modulated in space and time during single REM sleep episode, distinct from neocortical CFC. These findings extend the multiple criteria used to define REM sleep state in health and disease.